STIFEL 2026 HEALTHCARE CONFERENCE - IMMUNIC INC

Explicit Guidance:

• Runway: Current cash runway extends through mid-2028, contingent on the conversion of warrants associated with positive Insure-1 and Insure-2 readouts, which would provide an additional $200M (total potential proceeds from the February 2024 financing event).
• Timeline for Catalysts: Two Phase 3 pivotal trials (Insure-1 and Insure-2) in relapsing MS (RMS) are scheduled to read out in December.
• Future Financing: Management anticipates seeking additional financing options post-data readout to further strengthen the balance sheet.

Business-Segment Outlook:

• Product Portfolio (Vitaflutamase Calcium):
  • Commercial Build: Initiating preparations for an NDA filing if Phase 3 RMS readouts are positive.
  • Target Product Profile: Aiming for a "highly competitive" efficacy profile with 30% risk reduction in relapses (given or take) and robust MRI outcomes (referencing the Phase 2 78% reduction in gadolinium-enhancing lesions).
  • Safety Differentiation: Targeting a "home run" safety profile characterized by no liver signal, no serious/opportunistic infection imbalance, and minimal daily tolerability issues (nausea, diarrhea, flushing, alopecia) compared to current oral therapies.
• Pipeline Progression:
  • PROTECT-MS Study: Phase 3 trial in progressive MS (PMS) is initiating with first patient dosing expected in the first half of next year.
  • Study Specs: Approximately 1,400 patients powered on time-to-worsening (9-hole peg test).
  • Strategic Rationale: Building on the CALIPER Phase 2 study, specifically targeting the non-active/non-relapsing population where current therapies (e.g., Ocrelizumab) show limited efficacy.

Market and Competitive Outlook:

• Addressable Populations:
  • Oral Therapy Preferrers: Capturing the 25–30% of the MS market preferring oral DMTs despite current tolerability limitations.
  • Anti-CD20 Switchers: Targeting ~40,000 patients (approx. 25% of the anti-CD20 cohort) actively seeking to discontinue broad B-cell depletion due to long-term safety concerns or progression.
  • Older Demographics: Focusing on the 40–50% of RMS patients aged 55+, who face unique risks with potent immunosuppressants due to immunosenescence and polypharmacy.
• Competitive Positioning:
  • Vs. Current Orals: Expecting to compete against fumarates and S1P modulators (e.g., Tecfidera, Gilenya) based on efficacy/safety balance rather than just ARR.
  • Vs. BTK Inhibitors (e.g., Rimabrutinib): Anticipated differentiation in patients switching from anti-CD20s or older patients due to concerns over BTKi class effects (bleeding risks, infection imbalance, drug-drug interactions).
  • Market Dynamics: Viewing the MS space as "ripe" for a new entrant (citing TG Therapeutics as an analog) with only three active companies currently (Novartis, Roche, TG).
• Pricing & Reimbursement:
  • Pricing Strategy: Aiming for ~$115,000 USD annual WAC (consistent with current branded oral DMTs), with estimated 30% gross-to-net discounts.
  • Step Therapy: Expecting no mandatory step therapy failures against generic teriflunomide (Aubagio) due to distinct mechanisms (NLRP1 activation + selective DHODH inhibition) and superior safety profile.

Macro / Industry Outlook:

• Payer Environment: Anticipates maintaining high net pricing and specialty pharmacy status, noting that even with generic competition in the class, a 50-50 split between branded and generic usage persists.
• Demographic Shifts: The MS patient population is aging and healthier (younger diagnosis), leading to lower event rates in trials and changing treatment needs over time.

Strategic Initiatives:

• Commercial Model: Executing a targeted sales force approach, significantly leaner than historical models (historically 200–300 reps; new force will be "much lower" in headcount), focusing on the ~3,000 clinicians writing 80% of prescriptions.
• Talent Acquisition: Committing to hiring top-tier talent from established competitors to lead commercial execution.
• Mechanism Validation: Aggressively pursuing the NLRP1 (neuroprotection) narrative, betting on the CALIPER Phase 2 signal in non-active progressive MS to justify the PROTECT-MS study.

Risks and Headwinds to Outlook:

• Clinical Trial Failure: Primary risk lies in the December Phase 3 RMS readouts; failure to meet relapse/MRI endpoints or safety thresholds would erode the NDA filing pathway.
• Statistical Power Constraints: Acknowledgment that progression endpoints in RMS studies are statistically challenging to achieve significance within 18-month trials; progression data will rely on the dedicated PROTECT-MS PMS trial.
• Cross-Study Comparisons: Difficulty in comparing efficacy to historical data (e.g., Abio, Tecfidera) due to evolved patient populations with lower relapse rates.
• Safety Signals: While Phase 2 data was robust, Phase 3 safety remains the critical variable for market adoption (specifically infection rates and tolerability vs. current standards).

Management Tone on the Future:

• Confidence Level: High confidence in the safety/tolerability profile ("never seen anything quite like this") and the neuroprotective potential (NLRP1).
• Hedges: Management explicitly notes that the RMS trials are not powered for progression and that failure to see a "screaming p-value" on progression endpoints in RMS data would not necessarily undermine confidence in the NLRP1 mechanism, as the PROTECT-MS study is the primary vehicle for this proof.
• Competitive Stance: Optimistic that Vitaflutamase Calcium and Rimabrutinib can coexist and thrive, with potential for sequential use over a patient's 40-year disease journey.

Miscellaneous:

• Mechanism Specifics: Drug is a dual-mechanism agent: NLRP1 activator (neuroprotection) and selective DHODH inhibitor (neuroinflammation).
• Warrant Convertibility: The February 2024 financing included warrants that are triggered to convert into cash upon positive Insure-1 and Insure-2 data.